1. Leukemia
Maturation of Myeloid Cells
Dr. Rania Alhady

2. Leukemia Dr. Rania Alhady Definition: Classification of leukemia:
Leukemias are a group of disorders characterized by the accumulation of malignant white cells in the bone marrow and blood.
• Abnormal cells cause symptoms because of:
(i) bone marrow failure (i.e. anemia, neutropenia, thrombocytopenia) and
(ii) infiltration of organs (e.g. liver, spleen, lymph nodes, meninges, brain, skin or testes).
Classification of leukemia:
1- Acute Leukemia:
Acute lymphoblastic leukemia: L1 – L3.
Acute myeloid leukemia: M0 – M7.
2- Chronic Leukemia:
Chronic lymphocytic leukemia.
Chronic myeloid leukemia.
Dr. Rania Alhady

3. Acute leukemia Acute Leukemia: Dr. Rania Alhady Definition: Etiology:
Clonal malignant disorders characterized by:
Uncontrolled proliferation of abnormal blast cells in bone marrow, and
Impaired production of normal blood cells.
Blast cells infiltrate peripheral blood and bone marrow.
Blast cells in bone marrow must be > 30% to diagnose acute leukemia.
Etiology:
1- Congenital disorder:
Down syndrome.
Immunodeficiency syndrome.
2- Ionizing radiation: X-ray, radiotherapy.
3- Chemicals: (alkylating agent, Benzene).
4- Viruses:
Human T-lymphocyte leukemia virus (HTLV1), Herpes virus, EBV.
Dr. Rania Alhady

4. Acute leukemia Dr. Rania Alhady Results: Classification:
* Chromosomal abnormality:
Imbalance between oncogene and anti-oncogene.
* Blast cells: Uncontrolled proliferation of this clone results in:
1- Arrest of cellular differentiation.
2- Reduced apoptosis.
3- Inhibition of normal marrow elements.
Classification:
Acute leukemias are classified according to the type of blast cells into:
ALL: Childhood leukemia.
AML: Adulthood leukemia.
Acute leukemias are fatal if not treated.
However, acute leukemias are easier to treat than chronic leukemias.
Dr. Rania Alhady

5. Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia (ALL):
It is the result of clonal proliferation of lymphoid progenitor cells originating in the marrow.
Incidence:
Under 10 – 15 years (Childhood onset)
Can be either B-cell ALL or T-cell ALL.
• B-cell ALL or T-cell ALL can be further classified into subtypes according to the moderate splenomegaly, hepatomegaly and meningeal syndrome.
Classification of acute lymphoblastic leukemia (ALL) according to the French-American-British (FAB) groups
Dr. Rania Alhady

6. Acute Lymphoblastic Leukemia
Clinical features:
1- Bone marrow failure:
RBCs → Anemia: pallor, lethargy, malaise and dyspnea.
Leukocytes → neutropenia: fever, malaise, features of mouth, skin, respiratory infections.
Platelets → throbombocytopenia: spontaneous bruises, pupura, bleeding gums.
2- Tissue infiltration:
L.N. enlargement.
Hepatomegaly More common with ALL than AML.
Splenomegaly.
3- Organ infiltration:
A- Bony infiltration.
B- Testicular infiltration.
C- C.N.S. infiltration.
4- Fever.
Dr. Rania Alhady

7. Acute Lymphoblastic Leukemia
Investigations:
1- CBC:
60% of patients have an elevated ↑↑ WBCs.
RBCs: ↓ Hb
Platelets: ↓
Neutrpenia
90% have lymphoblasts in the peripheral blood film.
2- Bone marrow:
BM Aspirate:
Hypercellular BM
All normal marrow elements are depressed and replaced by abnormal blasts.
30% or more of all nucleated cells are blast
B. BM Biopsy:
Indicated in:
If aspirate is: a- Difficult. b- Hypercellular
Follow up.
Dr. Rania Alhady

8. Acute Lymphoblastic Leukemia
FAB Classification: L3 L2 L1
Homogenous
Heterogenous in size and shape
Cell population
Large
Small & Large
Small
Cell Size ↓ ↑
N/C ratio
Prominent
Prominent (1 - 2)
Inconspicuous
Nucleoli
Basophilic with vaculations
Larger
Scanty
Cytoplasm 1%
14%
85%
Child
Age 9%
60%
31%
Adult
Dr. Rania Alhad y

9. Acute Lymphoblastic Leukemia
Morphological classification of ALL L1 L2 L3
(a) L1 subtype-blasts show scanty cytoplasm without granules.
(b) L2 subtype-blasts are larger and heterogeneous with more abundant cytoplasm.
(c) L3 subtype-blasts are deeply basophilic with cytoplasmic vacuolation.
Dr. Rania Alhady

10. Acute Lymphoblastic Leukemia
3- Immunophenotyping:
Antigen present in the cell membrane
A- Myeloid markers: -ve CD13, CD33
B- Pan B markers: +ve CD19, CD20, CD22
C- Pan T markers: +ve CD2, CD5, CD7
4- Cytogenetics:
• Philadelphia chromosome translocation t(9; 22): may occur and results in poor prognosis.
5- Cytochemistry:
Chemical activity of the cell.
Myeloperoxidas, Sudan Black B, Non-specific estrase: -ve
Acid phosphatase: +ve in T-ALL
PAS (periodic acid shiff): +ve
Dr. Rania Alhady

11. Acute Lymphoblastic Leukemia
6- Radiology:
CXR: mediastinal mass (T-cell ALL)
Osteopenia or lytic lesion 50% of patients with ALL.(itractable pain).
Prognosis of ALL:
Bad prognosis in:
WBCs: ↑ >
Sex: boys due to testicular involvement.
Serum Ig ↓ (also ↑ incidence of T-ALL)
L2 & L3 morphology.
Organomegaly
Cytogenetic abnormalities
T-ALL
Dr. Rania Alhady

12. Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML):
Definition:
Clonal proliferation of myeloid precursor cells with reduced capacity to differentiate into more mature cellular elements.
Results in accumulation of leukemic forms in bone marrow, peripheral blood, and other tissues.
Leads to reduction in RBCs, platelets, PMNs.
It occurs in several morphologic variants; each one has a characteristic clinical & lab. features (M0 – M7)
Dr. Rania Alhady

13. Acute Myeloid Leukemia
Incidence:
AML is the most common leukemia in neonates.
80% of AML is in adults.
20% of AML is in children.
Diagnosis:
Clinical Picture:
Anemia  weakness and easy fatigue
Neutropenia  infections
Thrombocytopenia  gingival bleeding, ecchymoses, epistaxis, menorrhagia
Anorexia, weight loss, fever.
Organomegaly:
HSM in 1/3 of patients.
Lymphadenopathy is uncommon except in monocytic variants.
Dr. Rania Alhady

14. Acute Myeloid Leukemia
B. Laboratory diagnosis:
Bone Marrow Exam: Aspiration and biopsy
* Morphologic classification using cytochemistry and immunophenotyping
Cytochemistry:
Peroxidase: +ve
Sudan black: +ve
Specific esterase: +ve
Immunophenotyping: Pan myeloid markers: +ve CD13, CD33
* Cytogenetic analysis
* Evaluation for presence of significant fibrosis, presence of granulomata
Dr. Rania Alhady

15. Acute Myeloid Leukemia
Diagnosis requires all of the following diagnostic components:
Documentation of bone marrow infiltration
Myeloid origin of the leukemic cells
FAB/WHO classification of the leukemia
FAB Classifications
M0: minimally differentiated
M1: without maturation
M2: with maturation.
M3: promyelocytic.
M4: myelomonocytic.
M5: monoblastic
M6: erythroleukemia
M7: megakaryoblastic.
Dr. Rania Alhady

16. Acute Myeloid Leukemia
Dr. Rania Alhady

17. Acute Myeloid leukemia
Dr. Rania Alhady